The relationship of insulin deficiency to pancreatic alpha-cell dysfunction is examined in obese diabetic subjects. Resistance to glucagon suppression by glucose is studied with reference to reversibility with exogenous insulin administration and following weight loss in this group. Extensive investigations of the relationship between insulin deficiency and relative glucagon excess to gastrin dynamics and gastric acid secretion in obese and lean diabetic patients are contemplated. This is done to test the hypothesis that diabetes has a protective effect on the development of peptic ulcer disease. Similar studies of insulin-glucagon-gastrin interrelationships in patients with primary hyperparathyroidism are performed since we have shown that hyperinsulinemia exists in this disorder, and the incidence of peptic ulcer disease is known to be increased. In vitro studies of cultured pancreatic islets are undertaken to determine if sex steroids have direct effects on islet release of insulin and glucagon and how this relates to hormonal disturbances observed in islets obtained from pregnant and sex steroid rats. Hyperlipidemas observed in these conditions are correlated with alterations of tissue lipoprotein lipase activity, release and synthesis and hepatic apolipoprotein synthesis. A pilot study is proposed in order to develop an in vitro model for studying virus infection of pancreatic islets affects alpha and beta cell performance.